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Background Prior studies have shown that precore mutations abolish and basal core promoter ( BCP) mutations down-regulate hepatitis B e antigen ( HBeAg) production. Thus, the presence of precore and BCP mutations in HBeAg-positive patients indicates an infection with a mixed viral population of wild-type and precore and/or BCP mutant hepatitis B virus ( HBV). To date, there has been limited study of the prevalence and clinical significance of precore and BCP mutations in patients with HBeAg-positive chronic hepatitis B. Aim To determine the prevalence, predictors and clinical characteristics of mixed wild-type and precore/ BCP HBV infection, through a cross-sectional study, in a US cohort of patients with chronic hepatitis B. Methods We conducted a retrospective study of 828 chronic hepatitis B patients with HBV genotype and mutation panel testing seen at three US gastroenterology and liver clinics from June 2005 to September 2009. Results A majority of our patients (92.3%) were either Vietnamese or Chinese American. In the HBeAg-positive cohort, 17% of patients had precore mutations only, 28% had BCP mutations only and 5% had both BCP and precore mutations. On multivariate analyses, HBV genotype C, increasing age, lower HBV DNA level and an ALT quotient >2 were independent predictors for the presence of precore and/or BCP mutations. Conclusions The current distinction and management recommendations for HBeAg-positive vs. HBeAg-negative patients with chronic hepatitis B should be reassessed. Additional biomarkers and treatment endpoints should be studied for their usefulness in predicting continued viral suppression after treatment discontinuation. [ABSTRACT FROM AUTHOR]

Background One of the most important factors in treatment failure using nucleos(t)ide analogues in chronic hepatitis B is anti-viral resistance. Primary drug resistance refers to amino acid changes in the hepatitis B virus polymerase/reverse transcriptase (rt) that result in reduced susceptibility to anti-viral agents. Pre-existing drug resistance mutations may occur in untreated patients and may affect their treatment outcomes. Aim To determine the prevalence of hepatitis B DNA polymerase mutations in treatment-naïve patients. Methods We used a direct PCR sequencing test to detect DNA polymerase mutations in 472 consecutive treatment-naïve patients at two community gastroenterology clinics in Northern California. Results A majority of patients were Asians (>95%), had either genotype B or C (95%) and had no evidence of cirrhosis or liver cancer (94%). Mean age was 45 ± 13 and mean hepatitis B virus DNA was 5.3 ± 1.8 log10 IU/mL. Most patients did not have any detectable mutations (82.4%). Some (16.7%) had mutations of unknown clinical significance (rtV207M/L/I) and only 4 patients had rtA181A/S, rtA194S or M250I. Conclusions No rtM204V/I or rtN236T mutations were observed in our study. Less than 1% of our patients had mutations that can be associated with primary resistance to existing anti-viral therapies for hepatitis B virus. [ABSTRACT FROM AUTHOR]